Our long term objective is to understand the molecular mechanisms involved in the transformation of the budding yeast form to the filamentous form of the pathogen Candida albicans. Recently evidence was presented which suggested that budding cells could not be induced to transform to the invasive pseudo-mycelial form unless they first stopped multiplying and entered stationary phase, where they accumulated as unbudded cells at a stage early in the cell cycle. In addition, once a stationary phase cell had formed a pre-bud or a pre-tube evagination, it was then committed to bud or limited pseudo-mycelium formation respectively. The commitment events may be related to the temporal and spacial regulation of primary septum formation. Our specific research objectives are related to the regulation of germ tube inducibility and commitment. First, we will investigate the nature of the autoinhibitor released by cells in growth cultures which regulates the final cell concentration and which may be responsible for the acquisition of the capacity to form a pseudo-mycelium. Second, we will examine whether cells must stop multiplying and whether they must accumulate at a specific point in G1 of the cell cycle before they can be induced to form pseudomycelia. Third, we will investigate whether commitment to either growth form represents a decision concerning the position and timing of septation. This portion will involve a detailed biochemical and electron-micrographic analysis of the temporal and spacial regulation of chitin synthetase during synchronized bud and germ tube outgrowth. Fourth, we will attempt to isolate temperature sensitive mutants which either do not form germ tubes or which form aberrant germ tubes.